1-247896121-C-T

Position:

• chr1-247896121-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001001957.2(OR2W3):​c.535C>T​(p.Arg179Cys) variant causes a missense change. The variant allele was found at a frequency of 0.507 in 1,613,738 control chromosomes in the GnomAD database, including 213,360 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.43 (15702 hom., cov: 33)
  • Exomes 𝑓: 0.52 (197658 hom.)
• Consequence: OR2W3 NM_001001957.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.59

Genes affected

OR2W3 (HGNC:15021): (olfactory receptor family 2 subfamily W member 3) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.8534534E-5).
• BP6: Variant 1-247896121-C-T is Benign according to our data. Variant chr1-247896121-C-T is described in ClinVar as [Benign]. Clinvar id is 1582338.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2W3	NM_001001957.2	c.535C>T	p.Arg179Cys	missense_variant	1/1	ENST00000360358.3	NP_001001957.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2W3	ENST00000360358.3	c.535C>T	p.Arg179Cys	missense_variant	1/1		NM_001001957.2	ENSP00000353516	P1

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65665 AN: 151958 Hom.: 15702 Cov.: 33

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.444

GnomAD3 exomes AF: 0.480 AC: 120564 AN: 251182 Hom.: 30348 AF XY: 0.486 AC XY: 65922 AN XY: 135756

Gnomad AFR exome AF: 0.217

Gnomad AMR exome AF: 0.353

Gnomad ASJ exome AF: 0.511

Gnomad EAS exome AF: 0.564

Gnomad SAS exome AF: 0.421

Gnomad FIN exome AF: 0.578

Gnomad NFE exome AF: 0.536

Gnomad OTH exome AF: 0.495

GnomAD4 exome AF: 0.515 AC: 753060 AN: 1461662 Hom.: 197658 Cov.: 61 AF XY: 0.513 AC XY: 373340 AN XY: 727152

Gnomad4 AFR exome AF: 0.220

Gnomad4 AMR exome AF: 0.355

Gnomad4 ASJ exome AF: 0.511

Gnomad4 EAS exome AF: 0.508

Gnomad4 SAS exome AF: 0.419

Gnomad4 FIN exome AF: 0.573

Gnomad4 NFE exome AF: 0.537

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.432 AC: 65672 AN: 152076 Hom.: 15702 Cov.: 33 AF XY: 0.431 AC XY: 32079 AN XY: 74348

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.560

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.445

Alfa AF: 0.513 Hom.: 50557

Bravo AF: 0.411

TwinsUK AF: 0.545 AC: 2021

ALSPAC AF: 0.540 AC: 2081

ESP6500AA AF: 0.231 AC: 1016

ESP6500EA AF: 0.532 AC: 4576

ExAC AF: 0.477 AC: 57943

Asia WGS AF: 0.482 AC: 1678 AN: 3478

EpiCase AF: 0.538

EpiControl AF: 0.531

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	15
DANN	Benign	0.13
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.000039	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-4.2	N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.39	T
PROVEAN	Benign	12	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.066
ClinPred		0.018	T
GERP RS		4.2
Varity_R		0.048
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10888267; hg19: chr1-248059423; COSMIC: COSV64456045;